As part of a program in which the enzymes that participate in the process of detoxication are being examined as to their catalytic mechanism, attention is being concentrated on the properties of two enzymes. One is a sulfotransferase (aryl sulfotransferase IV) which serves as a model for sulfotransferases in that it catalyzes the transfer of the sulfuryl group from 3-phosphoadenosine 5- phosphosulfate (PAPS) to a broad range of phenols; the products are 3- phosphoadenosine 5-phosphosulfate and the corresponding phenylsulfate. The enzyme has been cloned from rat liver and is expressed in very large quantities with E. coli. Expression, however, yields two different enzyme forms, only one of which, form B, is active in the physiological reaction, i.e. the formation of a phenylsulfate from PAPS. Labeled as forms A and B, both catalyze the reverse reaction, i.e. the formation of free phenol in the presence of PAP. It seems that PAP is bound to enzyme so tightly in form A, that the physiological donor, PAPS, is prevented from binding to the enzyme. Upon oxidation of protein thiols, PAP is released and the two forms of the enzyme can be interconverted. The effects oxidation and reduction of protein thiols appear to be physiological control mechanism for detoxication of phenols under conditions of oxidative stress. The detoxication process, i.e. the process that leads to excretion of toxic compounds, can, paradoxically, produce very toxic compounds. Ethylene carbonate, a cyclic carbonate, has been implicated in the production of toxic symptoms very much like those found after adulteration of wine with ethylene glycol. We have isolated and purified to homogeneity an enzyme from rat liver, cyclic carbonate hydrolase, which hydrolyzes the carbonate to carbon dioxide and ethylene glycol. Catalysis is limited to hydrolysis of cyclic carbonates; linear carbonates are inactive. Partial sequence analysis suggests a relationship of the protein to a developmental growth factor.